CAR macrophage-like cells from stem cells show tumor response but limited persistence in mice

Researchers at Kyoto University's CiRA created CAR macrophage-like cells from expandable pluripotent stem cell-derived myeloid lines, showing tumor response in vitro and in mice, but the cells disappeared within 7 days after administration, highlighting limited persistence as a key challenge. The team generated doxycycline-inducible anti-HER2 CAR macrophages from two human stem cell lines. In vitro, these cells reduced HER2-positive tumor signals and engulfed tumor cells. RNA sequencing distinguished transcriptional responses from tumor contact versus CAR induction, with the latter emphasizing vesicle transport and lysosome pathways. In mouse co-transplantation assays, both CAR-induced and non-induced cells suppressed tumor growth versus untreated controls, but no significant added benefit from CAR induction was observed, and all mice eventually died. The administered cells' signal declined by day 3 and vanished by day 7, indicating that optimizing cell supply and post-administration persistence requires separate strategies.